The long-term objective of this project is to elucidate the neuronal mechanisms of learning and memory in the marine mollusk Aplysia californica. The defensive withdrawal reflex of this animal constitutes a useful system for this purpose. The reflex exhibits several forms of learning, including classical conditioning. The neuronal circuitry which underlies the withdrawal reflex, particularly its monosynaptic component- the synapse between the sensory and motor neurons-is relatively simple and well understood. The proposed experiments will focus on a form of synaptic plasticity known as Hebbian long-term potentiation (LTP). This form of synaptic plasticity, particularly its manifestation in the CA1 region of the hippocampus, has been prominently implicated in vertebrate memory and cognition. Recently, a type of LTP has been described for Aplysia sensorimotor synapses in cell culture (apLTP) which appears to be mechanistically quite similar to LTP of CA1 synapses. The specific aim of this proposal is to deterMine whether an apLTP-related process is involved in learning in Aplysia. The proposed experiments will utilize preparations comprising the central nervous system of Aplysia in electrophysiological experiments involving a cellular analogue of classical conditioning of the withdrawal reflex. The proposed research will serve as the basis for improving our understanding of human learning and memory. It may thereby contribute to ameliorating human memory- associated diseases, such as Alzheimer' s.